{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T11:35:23Z","timestamp":1786448123163,"version":"build-2736575974"},"reference-count":50,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82304889"],"award-info":[{"award-number":["82304889"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82304889"],"award-info":[{"award-number":["82304889"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Shaanxi Fundamental Science Research Project for Mathematics and Physics","award":["25JSQ029"],"award-info":[{"award-number":["25JSQ029"]}]},{"DOI":"10.13039\/501100011269","name":"Ministry of Education","doi-asserted-by":"publisher","award":["2026FTMP005"],"award-info":[{"award-number":["2026FTMP005"]}],"id":[{"id":"10.13039\/501100011269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009103","name":"Shaanxi Provincial Department of Education","doi-asserted-by":"publisher","award":["24JS010"],"award-info":[{"award-number":["24JS010"]}],"id":[{"id":"10.13039\/501100009103","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009103","name":"Shaanxi Provincial Department of Education","doi-asserted-by":"publisher","award":["25JK0084"],"award-info":[{"award-number":["25JK0084"]}],"id":[{"id":"10.13039\/501100009103","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009103","name":"Undergraduate and Higher Continuing Education Teaching Reform Research Project of Shaanxi Province","doi-asserted-by":"publisher","award":["25ZY007"],"award-info":[{"award-number":["25ZY007"]}],"id":[{"id":"10.13039\/501100009103","id-type":"DOI","asserted-by":"publisher"}]},{"name":"TCM Science and Technology Innovation Research Team Project","award":["2025-CXTD-03"],"award-info":[{"award-number":["2025-CXTD-03"]}]},{"name":"Key Laboratory of Environment-related Diseases and TCM Prevention and Control"},{"name":"Qiling Liu"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bioengineering"],"abstract":"<jats:p>Osteoarthritis is an irreversible degenerative joint disease driven by sustained NF-\u03baB-mediated inflammatory responses, and conventional intra-articular hyaluronic acid or small-molecule NF-\u03baB inhibitors cannot achieve targeted on-demand treatment due to poor solubility, rapid clearance and lack of lesion microenvironment responsiveness. OA with inherent anti-chondrolytic activity can self-assemble into nanocarriers in water, yet it lacks stimuli-responsive capacity. Herein, we rationally designed and synthesized an OA-Der by covalently conjugating o-phenylenediamine fragments to the OA backbone. 1H NMR and HRESI-MS spectra fully verified the accurate chemical structures of intermediate and final OA-Der. Blank OA-Der micelles exhibited uniform spherical core\u2013shell nanostructures (50\u2013150 nm) under TEM and AFM, while pathological high NO triggered complete disassembly of micellar assemblies. We further co-assembled OA-Der with NF-\u03baB inhibitor BAY 11-7082 to construct NO-responsive BAY@OA-Der supramolecular micelles. In vitro experiments using human C28\/I2 chondrocytes with LPS-induced inflammatory injury demonstrated that BAY@OA-Der significantly improved cell viability and reduced apoptotic chondrocyte proportion. At mRNA and protein levels, the supramolecular micelle formulation remarkably suppressed NF-\u03baB p65 phosphorylation, downregulated cartilage-degrading ADAMTS5, and upregulated ACAN compared with free BAY or blank OA-Der. Collectively, this natural bioactive self-assembled NO-responsive delivery platform achieves synergistic anti-inflammatory and matrix-protective effects by precisely releasing drugs at NO-overexpressed osteoarthritis inflammatory sites and offers an in vitro design strategy for osteoarthritis responsive delivery systems.<\/jats:p>","DOI":"10.3390\/bioengineering13080908","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T10:32:16Z","timestamp":1786444336000},"page":"908","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["NO-Responsive Oleanolic Acid Self-Assembled Micelles Co-Loaded with BAY 11-7082 for Synergistic Chondroprotection and Anti-Osteoarthritis Therapy"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8659-7359","authenticated-orcid":false,"given":"Dandan","family":"Zhang","sequence":"first","affiliation":[{"name":"School of Public Health, Shaanxi University of Chinese Medicine, Xianyang 712046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhigang","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Public Health, Shaanxi University of Chinese Medicine, Xianyang 712046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dingxing","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Public Health, Shaanxi University of Chinese Medicine, Xianyang 712046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4405-7391","authenticated-orcid":false,"given":"Zhuoran","family":"Sun","sequence":"additional","affiliation":[{"name":"School of Clinical Medicine, Shaanxi University of Chinese Medicine, Xianyang 712046, China"},{"name":"Xianyang Central Hospital, Xianyang 712000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiamin","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Public Health, Shaanxi University of Chinese Medicine, Xianyang 712046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Public Health, Shaanxi University of Chinese Medicine, Xianyang 712046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingyang","family":"Zeng","sequence":"additional","affiliation":[{"name":"School of Public Health, Shaanxi University of Chinese Medicine, Xianyang 712046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiling","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Public Health, Shaanxi University of Chinese Medicine, Xianyang 712046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9774-5823","authenticated-orcid":false,"given":"Wenzhuo","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Functional Textile Material and Product, Ministry of Education, School of Environment and Chemical Engineering, Xi\u2019an Polytechnic University, Xi\u2019an 710048, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,11]]},"reference":[{"key":"ref_1","first-page":"152","article-title":"The epidemiology, etiology, diagnosis, and treatment of osteoarthritis of the knee","volume":"107","author":"Michael","year":"2010","journal-title":"Dtsch. 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